Dissociation of basal turnover and cytokine-induced transcript stabilization of the human cyclooxygenase-2 mRNA by mutagenesis of the 3'-untranslated region.
The immediate early gene cyclooxygenase-2 (Cox-2), which encodes the inducible prostaglandin synthase enzyme, is regulated at the level of post-transcriptional mRNA turnover. In this study, the functional role of the 3'-untranslated region (3'-UTR) of the human Cox-2 gene was characterized. Deletion of the distal region of the 3'-UTR strongly inhibited basal mRNA turnover, suggesting that this region contains mRNA instability determinants. However, deletion of the proximal highly-conserved region (CR1: 6082-6198) resulted in increased basal turnover, indicating that it determines mRNA stability. All of the 3'-UTR constructs conferred IL-1-induced stabilization but not dexamethasone-induced down-regulation. Thus, distinct regions of the 3'-UTR of the Cox-2 transcript are involved in the regulation of basal and cytokine-induced mRNA metabolism.
Gou
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Department of Physiology, University of Connecticut School of Medicine, Farmington 06030, USA.
Liu
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CH
Ben-Av
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Hla
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D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D016296:Mutagenesis / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D003609:Dactinomycin; D003907:Dexamethasone; D008156:Luciferases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases